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细胞因子诱导的杀伤细胞辅助的肿瘤靶向递送:携带近红外光敏剂的Her-2单克隆抗体偶联金纳米星用于增强癌症治疗

Cytokine-induced killer cells-assisted tumor-targeting delivery of Her-2 monoclonal antibody-conjugated gold nanostars with NIR photosensitizer for enhanced therapy of cancer.

作者信息

Liang Shujing, Sun Menglin, Lu Yonglin, Shi Shuo, Yang Yiting, Lin Yun, Feng Chan, Liu Jie, Dong Chunyan

机构信息

Breast Cancer Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, P. R. China.

Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai 200092, P. R. China.

出版信息

J Mater Chem B. 2020 Sep 23;8(36):8368-8382. doi: 10.1039/d0tb01391a.

Abstract

Maximizing the accumulation of anticancer medicine in the tumor is the priority to achieve minimal invasive cancer therapy, which raises high demands on tumor-targeting ability of drug delivery systems. Herein, we adopted an emerging "cell-drug" strategy via the nanoplatform construction to achieve high aggregation and intratumoral distribution. We fabricated gold nanostars (GNSs) with HER-2 monoclonal antibody (trastuzumab) and near-infrared region (NIR) photosensitizer indocyanine green (ICG) to obtain GNS@ICG-Ab, which combined the photothermal therapy with photodynamic therapy (PTT/PDT) that rely on enhanced photothermal conversion efficiency of GNS and 1O2 generator ICG under the exposure of a NIR laser. Tumor-tropism CIK cells loaded with GNS@ICG-Ab were able to migrate into tumors and make a difference in efficient accumulation and uniform distribution of the GNS@ICG-Ab-CIK nanoplatform inside tumors based on fluorescence, photoacoustic (PA), and computed tomography (CT) imaging observations. Encouraged by the improvements in tumor targeting and retention presented by real-time imaging, we employed the novel nanoplatform to synergistically inhibit the progression of tumors in SK-BR-3 tumor-bearing mice via PTT/PDT and immunotherapy-implemented by CIK cells for activating the immune response, and with the specific linkage between trastuzumab and SK-BR-3 tumor cells, our platform could exert a precise strike of PDT/PTT. Taken together, the integrating tri-modal imaging with tri-modal therapy endows CIK-GNS@ICG-Ab with promising potential in cancer theranostics and lays a solid foundation for the development of immune cell application in nanomedicine delivery.

摘要

使抗癌药物在肿瘤中实现最大程度的蓄积是实现微创癌症治疗的首要任务,这对药物递送系统的肿瘤靶向能力提出了很高的要求。在此,我们通过构建纳米平台采用了一种新兴的“细胞-药物”策略,以实现高聚集和肿瘤内分布。我们用HER-2单克隆抗体(曲妥珠单抗)和近红外区域(NIR)光敏剂吲哚菁绿(ICG)制备了金纳米星(GNSs),以获得GNS@ICG-Ab,其将光热疗法与光动力疗法(PTT/PDT)相结合,该疗法依赖于在近红外激光照射下GNS增强的光热转换效率和1O2生成剂ICG。负载GNS@ICG-Ab的肿瘤嗜性CIK细胞能够迁移到肿瘤中,并基于荧光、光声(PA)和计算机断层扫描(CT)成像观察,使GNS@ICG-Ab-CIK纳米平台在肿瘤内实现高效蓄积和均匀分布。受实时成像所呈现的肿瘤靶向性和滞留性改善的鼓舞,我们采用这种新型纳米平台,通过PTT/PDT和由CIK细胞实施的免疫疗法协同抑制SK-BR-3荷瘤小鼠肿瘤的进展,以激活免疫反应,并且由于曲妥珠单抗与SK-BR-3肿瘤细胞之间的特异性连接,我们的平台可以对PDT/PTT进行精确打击。综上所述,将三模态成像与三模态治疗相结合赋予CIK-GNS@ICG-Ab在癌症诊疗方面具有广阔的潜力,并为免疫细胞在纳米医学递送中的应用开发奠定了坚实的基础。

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